Steroidal compounds and methods for obtaining the same



Patented Oct. 8, 1946 STEROIDAL COMPOUNDS AND FOR OBTAININ Romeo B. Wagner,

G THE SAME J r State College, Pa., assignor to OFFICE METHOD Parke, Davis & Company, Detroit, Mich., a cor:-

poration of Michigan No Drawing. Application May 15, 1944, I

Serial No. 535,754 r 11 Claims. (01. zoo-397.4)

This invention relates to the preparation of new compounds of the pregnane series which are oxygenated in the nuclear position 12. These compounds are useful intermediates in the preparation of hormone products.

In the copending Patent No. 2,352,852, issued July 4, 1944, a method was described by which steroidal sapogenins may be isomerized to pseudosapogenins and these pseudo-sapogenins further mildly oxidized and hydrolyzed to give 16-17 unsaturated 20 keto pregnane series compounds. The transformations may be indicated as follows:

Oxidation l and hydrolysis where S represents the rings A, B and C of the steroid nucleus and R is an acyl radical (R20 representing an acyl anhydride) I have now found that these reactions may also be applied to newly discovered steroidal sapogenins which are oxygenated in ring C at poition 12 and decribed in my copending application, Serial No. 535,759, filed May 15, 1944, and carrying as Well further hydroxyl substituents at positions 2 and 3, e. g, manogenin (2-hydroxy-l2- keto-tigogenin), agavogem'n (2,12-dihydroxy tigogenin), and mexogenin (2-hydroxy-12-keto smilagenin). The corresponding 'pseudo-sapogenins are described in my copending application, Serial No. 535,755, filed May 15, 1944.

The invention may be illustrated bythe following example:

16-alZo-pregnen-2,3 (,8) -dz'0Z-12,20-dz0ne. To a solution of 2 g. of pseudomanogenin triacetate in 30 cc. of acetic acid was added a solution of 1.2

g. chromic anhydride in 10 cc. of acetic acid. After the reaction mixture had stood at' 20 for ninety minutes it was diluted with water and the product was extracted with ether. The ethereal solution was washed free from acetic acid and evaporated. The residue was hydrolyzed with 2 alcoholic potassium hydroxide for thirty minutes. The hydrolysis mixture was-diluted with an equal volume of water and extracted with a large volume of ether (3-liters). The ether was removed and the residue was acetylated and crystallized from aqueous methanol as White plates, M. P. 264-267. This is 16-allo-pregnen-2,3(p) -di0l- 12,20-dione.

In the same manner pseudo-mexogenin yields 16-pregnene-2,3-diol-12,20-dione and pseudoagavogenin yields 16-allo-pregnene-2,3,12-triol- 20-one. If it is desired to use an ester in further processing of these hormone intermediates such derivatives may be prepared in the usual manner, e. g. by boiling with acid anhydride or by treatment with acid anhydride and pyridine at temperatures between 20 and C. In any case all hydroxyls acylate with about equal ease, there being essentially no qualitative difierence in reactivity.

.The transformations described may be illustrated as follows:

Pseudo-manogenin trlacylate (e g. triacetate) Oxidation I and Hydrolysis e 16al1o-pregnene-2,3-diol-12,20-dione 16-:111o-p1-egmone-234110142,20-diono diacylate (e. g. diacetate) CH1 CH'aGHi Pseudo-mexogenin triac ylate (e. g. triaoetate) Oxidationl andhydrolysis B50116. g: H'a M I 16-pregnene-2 3-dio1-12,20 dione.

diacylate (e. g. diacetat Pseudo-agavogenin tetra-acylete (e; g. tetra-acetate) Oxidation l and hydrolysis OH; CH: CH: 4:

HO l l H lfi-allo-pregnene-2,3,12-triol-one-20 R20 lle. E. L h I Rog 16-a11o-pregnome-2,3,12-trio1-20one aoylate (e. g. acetate) What I claim is: 1. A compound of the formula Z CH:

where Y is a member of the class and groups hydrolyzable to and Z is a. member of the class groups hydrolyzable to and =0.

2. A compound ofthe formula 0 CH; CH: CH1, o

where Y is a, member of the class 

